三硝基丙酸预处理对缺血-再灌注兔心肌细胞凋亡的影响

Preconditioning with 3-nitropropionic acid reduces myocardial apoptosis induced by ischemia-reperfusion injury

目的观察三硝基丙酸（3-NPA）预处理对缺血-再灌注兔心肌细胞凋亡的影响及其机制。方法24只新西兰大耳兔随机分为对照组（C组）、实验组（3-NPA组）和阻滞剂组（5-HD组），每组8只。5-HD组在开胸前24h通过耳缘静脉注射特异性线粒体ATP敏感钾通道阻滞剂5-羟基癸酸（5mg·k^-1），C组和3-NPA组注射同样体积的生理盐水。10min后3-NPA组和5-HD组注射3-硝基丙酸（3mg·kg^-1），C组注射同样体积的生理盐水。通过结扎兔左冠状动脉建立心肌缺血-再灌注动物模型，三组缺血30min再灌注120min。检测再灌注120min后心肌梗死面积、心肌细胞凋亡指数、Bcl-2和Bax蛋白的表达。对实验数据进行方差分析检验。结果3-NPA组的心肌梗死面积显著低于其它C组[（0．26±0．07）vs．（0．45±0．09），P〈0．01]和5-HD组[（0．26±0．07）vs．（0．40±0．07），P〈0．01]；C组和5-HD组之间没有显著性差异[（0．45±0．09）vs．（0．40±0．07），P〉0．05]。3-NPA组心肌细胞凋亡指数明显小于C组[（27．72±5．18）vs．（45．91±10．54），P〈0．01]和5-HD组[（27．72±5．18）vs．（43．44±7．33），P〈0．01]。3-NPA组bcl-2表达高于另外两组[（0．123±0．046）vs．（0．079±0．019），（0．080±0．019），P〈0．05]，而Bax明显低于另外两组[（0．095±0．020）vs．（0．14±0．05）and（0．15±0．05），P〈0．05]。结论3-NPA预处理对缺血-再灌注心肌具有良好的抗凋亡作用，这与其开放断线粒体ATP敏感钾通道有关。

Objective To investigate the effects of preconditioning with 3-nitropropionic acid on myocardial apoptosis induced by ischemia-reperfusion injury. Method Twenty-four rabbits were randomly divided into control group （group C, n = 8）, precondition group （group 3-NPA, n = 8） and 5-HD group （group 5-HD, n = 8）. The group 5-HD was treated intravenously with 5 mg·kg^-1 5-HD （ATP-sensitive potassium channels blocker）, group C and group 3-NPA received normal saline instead of 5-HD. Ten minutes later, 5-HD group and 3-NPA group were injected with 3-NPA （3 mg·kg^-1） and the group C was injected with normal saline. Twenty-four hours later, the left anterior descending coronary artery was ligated for 30 min and then unclamped for 120 min to establish ischemia-reperfnsion injury model. After reperfusion, the infarct sizes of ventricular myocardium, apoptotic myocardial cells and the expressions of Bcl-2 and Bax protein were measured. Results Infarct sizes and apoptotic myocardial cells in group 3-NPA were less than those in the others （ P 〈 0.01）. The expressions of Bcl-2 in group 3-NPA increased as compared with group C （P 〈 0.05） and group 5-HD （P 〈 0.05）, whereas the expressions of Bax in group 3-NPA decreased as compared with group C （ P 〈 0.05） and group 5-HD （ P 〈 0.05）. Conclusions Preconditioning with 3-nitropropionic acid reduces myocardial apoptosis induced by ischemia-reperfusion injury which is attributed to the opening of mitochondrial KATP channels.